Persistence of isolated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse – a European pooled analysis.

Abstract

#304 Purpose:
 The prognostic significance of DTC in the BM of breast cancer pts at the time of primary diagnosis has already been confirmed by a large pooled analysis. In view of the lack of early indicators for secondary adjuvant treatment, we here evaluated whether the persistence of DTC after adjuvant therapy confers a risk for relapse and breast cancer-related death.
 Patients and Methods:
 We analyzed BM aspirates of 723 pts from academic breast cancer units in Oslo (n=356), Munich (n=228) and Tuebingen (n=139) during recurrence-free follow-up at a mean interval of 31.7 months (standard deviation [std] 19.4 months) after primary diagnosis of breast cancer pT1-4, pN0-3 pM0. Carcinoma cells were detected using a standardized immunoassay with the monoclonal antibodies A45-B/B3 (Munich, Tuebingen), or AE1 and AE3 (Oslo), directed against cytokeratin (CK). Pts were followed for a median of 54.5 months (SD 25.1 months) after primary diagnosis.
 Results:
 Persistent DTC in the BM was detected in 15.5% of the pts (n=112). The Kaplan-Meier estimate for mean distant relapse-free survival was 162.5 months (157.9 – 167.0 95%CI) in pts with negative and 102.4 months (94.2 – 110.6, 95% CI, p< .0001, log rank test) in pts with positive BM status. The mean overall survival was 170.1 months, (167.7 – 172.5 95% CI), compared to 113.4 months in patients with persistent DTC in BM (107.3 – 119.5, p < .0001). In multivariate Cox regression analysis, allowing for BM status, tumor size, nodal status and histopathological grading, presence of DTC was an independent prognostic factor for reduced breast cancer specific survival ((RR 3.42, 1.64 – 7.13 95% CI, p= .001).
 Conclusion:
 Persistent DTC significantly predicts an increased risk for subsequent relapse, and, therefore, might serve as a potent monitoring tool for the follow-up of breast cancer pts. Future therapeutic intervention trials are currently being initiated to assess the benefit of secondary adjuvant treatment based on DTC detection as stratification parameter. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 304.

Advancing personalized cancer therapy by detection and characterization of circulating carcinoma cells

“…80,81,86 As evidenced by a European pooled analysis involving 696 breast cancer patients, persistence of DTC in 16% of breast cancer patients was an independent prognostic factor for subsequent reduced breast cancer survival. 87 The prognostic relevance of DTC detection in stage I to III breast cancer patients was shown recently, 88 and the presence of DTC in bone marrow was associated with a different pattern of locoregional cancer cell dissemination, obviously being influencing locoregional recurrence-free survival as well. 89 To implement screenings for MRD into clinical studies, besides other important requirements, repeated sample collection must be feasible.…”

“…CTC/DTC are able to survive chemotherapy and hormonal therapy 6,85 as well as to persist in bone marrow over many years post‐surgery, which is probably associated with an increased risk of late metastatic relapse 80,81,86 . As evidenced by a European pooled analysis involving 696 breast cancer patients, persistence of DTC in 16% of breast cancer patients was an independent prognostic factor for subsequent reduced breast cancer survival 87 . The prognostic relevance of DTC detection in stage I to III breast cancer patients was shown recently, 88 and the presence of DTC in bone marrow was associated with a different pattern of locoregional cancer cell dissemination, obviously being influencing locoregional recurrence‐free survival as well 89 …”

Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

“…Detection of micrometastases following adjuvant therapy has also been reported to correlate with a poor prognosis [ 32 ]. In a study exploring DTC, 723 patients underwent a bone marrow aspirate at a median of 32 months following primary diagnosis.…”

Clinical relevance and current challenges of research on disseminating tumor cells in cancer patients

“…A European pooled analysis involving 696 breast cancer patients revealed that the persistence of DTC in 16% of breast cancer patients was an independent prognostic factor for subsequent reduced breast cancer survival [75,76]. …”

“…The ability of DTC to survive chemotherapy and hormonal therapy [ 5 , 68 ] and the persistence in BM over many years post surgery, linked to an increased risk of late metastatic relapse, have been described previously [ 69 , 70 , 73 , 74 ]. A European pooled analysis involving 696 breast cancer patients revealed that the persistence of DTC in 16% of breast cancer patients was an independent prognostic factor for subsequent reduced breast cancer survival [ 75 , 76 ].…”